A novel anti-infective approach is to exploit stresses already imposed on invading organisms in vivo. Iron (Fe) metabolism is a key vulnerability of infecting bacteria because organisms require Fe for growth. We have shown that a strategy that uses the metal gallium (Ga) to disrupt bacterial Fe, metabolism holds promise as an antimicrobial approach. Due to its chemical similarity to Fe, Ga can substitute for Fe in many biologic systems and inhibit Fe-dependent processes. Our data shows that Ga kills the opportunistic pathogen Pseudomonas aeruginosa (including antibiotic resistant strains), is active against biofilms, and treats 3 different models of P. aeruginosa infections. Ga has also been shown to have anti-inflammatory properties. These data, the fact that gallium nitrate (trade name, GaniteTM) is Food and Drug Administration (FDA) approved for intravenous (IV) administration, and the dearth of new antibiotics in development make Ga a promising new therapeutic for P. aeruginosa infections. We have shown in our initial phase 1b study in patients with cystic fibrosis chronically infected with P. aeruginosa that IV Ga is safe, well tolerated, ha a good pharmacokinetic profile and is associated with a clinically meaningful improvement in lung function 14 days and 28 days after the start of a 5 day infusion of IV Ga. Here we propose a proof of concept phase 2 clinical trial to confirm our prior findings of efficacy and provide further data regarding the safety and pharmacokinetics of IV Ga in CF subjects infected with P. aeruginosa. We also propose two ancillary projects to further delineate the mechanism of action of this new agent. Chronic P. aeruginosa airway infections are the major cause of death in these patients and few treatments exist. This drug could represent a novel approach to treating this infection and have implications for other challenging infections.